Rate of Diffusion (flux) Concentration gradient substance x surface area of membrane x lipid solubility = Distance (thickness of membrane) x molecular weight Table 3-1: Factors Influencing the Rate of Net Diffusion of a Substance Across a Cell Membrane (Fick s Law of Diffusion) Constant in homeostasis Constant in homeostasis Constant in homeostasis for neutral molecules only Constant in homeostasis Constant in homeostasis The table indicates how changing the variable listed alone will alter diffusion rate. Table 3-1, p. 52 K + has a lower MW and is normally 30x more lipid soluble in most cell membranes than is Na + NEITHER HAS DIFFUSION COEFFICIENT OF 0, SO DIFFUSION WILL OCCUR ACROSS THE MEMBRANE IF THERE IS A CONCENTRATION GRADIENT
Diffusion through Ion Channels Ions such as Na +, K +, Cl, and Ca 2+ all use specific protein channels to diffuse into and out of cells. Channels are integral membrane proteins that span the lipid bilayer. A single protein may have a conformation that looks like a doughnut, with the hole in the middle providing the channel for ion movement. More often, several proteins aggregate, each forming a subunit of the walls of a channel. Specificity is determined by pore size of the channel, charge, and binding sites. 3 n through Ion Channe ls Fig. 4-5 4
Regulation of gated ion channel Temporary change in shape of protein changes status of ion channel Chemically regulated: a chemical messenger binds to a receptor that is a part of or associated with the ion channel A form of allosteric modulation gate opens/closes) Mechanically regulated: physical force alters the shape of the protein gate opens/closes Voltage regulated: distribution of charged particles in vicinity of gate alters shape of the protein opens/closes/locks(double gate) Osmosis: Diffusion of water Movement of solute (water) from high water concentration to low water concentration through a membrane that is permeable to water but not the solute molecules in it If the membrane was permeable to solute, it would come into equilibrium
Nonpenetrating Solute A solute that cannot go through a membrane lowers the water concentration of the solution Causes water to diffuse towards low water concentration Fig. 3-9, p. 52
Measurement of Osmolality of Human Plasma 1 mole of solute dissolved in 1 kg (1 liter) of H 2 O forms a 1 molal solution or 1000 milliosmolal solution ratio of solute particles (1 mole = 6.02 x 10 23 ) to solvent molecules the same in two different 1 molal solutions 18 grams H2O = 1 mole 1 liter = 1kg = 1000grams = 55.56 moles = 3.345 x 10 25 molecules H 2 O 1 mole of glucose = 180 grams glucose + 1 liter H 2 O = 1 molal glucose solution 1 mole of sodium = 23 grams sodium + 1 liter H 2 O = 1 molal sodium solution 1 mole of any solute per 1 liter water depresses freezing point of water by -1.86 o C Measurement of Osmolality of Human Plasma 1 m glucose freezes at -1.86 o C 1 m Na freezes at -1.86 o C 1 m NaCl freezes at -3.72 o C because NaCl ionizes to Na+ Cl- (twice as many particles = twice as many moles = 2 moles per liter water = 2 molal solution 0.5 NaCl freezes at -1.86 o C because NaCl ionizes to Na+ Cl- (twice as many particles = twice as many moles = 2x 0.5 moles per liter water = 1 molal solution m solution freezes at -0.93 o C m solution freezes at -0.62 o C m human plasma solution freezes at -0.56 o C
human ECF, ICF = 300mOSM Cells maintain osmotic equilibrium ECF, ICF have same osmotic pressure cells exposed to ECF, ICF, or 300milliosmal (0.3 Osm) solutions are in osmotic equilibrium when > 300milliosmolar, a solution is called hyperosmotic i.e. more osmotically active solute molecules than plasma when < 300milliosmolar, a solution is called hypoosmotic i.e. few osmotically active solute molecules than plasma when = 300milliosmolar, solution is isosmotic If exposure of a cell to a solution causes osmosis of water into or out from cell, regardless of the solution s osmolality then different terms are employed to avoid confusion. isotonic: does not influence osmosis hypertonic: causes cell to lose water (dehydrate, crenate) hypotonic: causes cell to gain water (swell, burst) human ECF, ICF = 300mOSM Cells maintain osmotic equilibrium ECF, ICF have same osmotic pressure cells exposed to ECF, ICF, or 300milliosmal (0.3 Osm) solutions are in osmotic equilibrium when > 300milliosmolar, a solution is called hyperosmotic i.e. more osmotically active solute molecules than plasma when < 300milliosmolar, a solution is called hypoosmotic i.e. few osmotically active solute molecules than plasma when = 300milliosmolar, solution is isosmotic
Solutes eaten but not absorbed can become osmotically active particles and create a hypertonic fluid compartment in the lumen of the gastrointestinal tract what happens to fluid volume of g.i. tract? Why is gargling salt water effect in treating a sore throat which is caused by pesky isotonic bacteria? Tonicity Tonicity of a solution Determines whether cell remains same size, swells, or shrinks when a solution surrounds the cell Isotonic solution (Cell remain the same size) Hypotonic solution (Cell swell) Hypertonic solution (Cell shrinks)
Fig. 3-13, p. 56 Extracellular Osmolarity & Cell Volume
Assisted Membrane Transport Outside energy source and/or protein assisted transport ASSISTED CLASSIFIED BY Energy Source Random molecule motion coupled with protein carrier facilitated diffusion Random molecular motion coupled with regulated ion channel Chemically regulated, mechanically regulated, voltage regulated ion channels ATP expenditure coupled with protein carrier Primary Active Transport (ATPase Pumps) Secondary Active Transport ATP expenditure coupled with vescicular activity Endocytosis Exocytosis ASSISTED CLASSIFIED BY (protein) Carrier-mediated transport Membrane carrier protein changes its shape Membrane channel protein changes its status (closed or open) Primary (1 ) active transport involves the direct expenditure of energy in the form of adenosine triphosphate (ATP) hydrolysis and carrier phosphorylation to transport an ion against the diffusion ATP + protein gradient (ATPase ADP + phosphorylated transporters) protein 1. Covalent phosphorylation by ATPase changes conformation of carrier protein (ATPase pump) until phosphate is removed by phosphatase activity; 2. two distinct conformations allow transported molecule(s) to bind as affinity with binding site(s) effected by presence/absence of phosphate group 3. Attracted molecule(s) are also transported through membrane as protein conformation changes 4. w/o ATP ADP + P i for phosphorylation of carrier, no shape change or molecule binding so no transport occurs, which is bad for cell
Concentration gradient Carrier 5 reverts to its original conformation and affinity. Plasma membrane ECF ICF Ion to be transported Binding site Carrier protein 1 Carrier protein s ase activity splits ATP into ADP plus phosphate. Phosphate group binds covalently to carrier, increasing affinity of its binding site for ion. 2 Ion to be transported binds noncovalently to carrier on lowconcentration side. 4 Carrier releases ion to side of higher concentration. Phosphate group is also released (phosphatase activity). Direction of transport Fig. 3-16, p. 59 3 In response to ion binding, carrier changes conformation and binding site is faces opposite side of membrane. The change in conformation reduces affinity of site for ion. 1. Binding of ligand stimulates phosphorylation 2. Change in carrier s conformation 3. Expulsion of ligand on opposite side; 4. Release phohsphate by phosphatase 5. Restore orginal shape 6. Bind next ligand (back to 1)
Active Transport (Primary Active Transport) Secondary Active Transport http://biomedicum.ut.ee/armpgb/1kursus/ani_6.swf On this site you can choose to view animations of either primary or secondary active transport Secondary Active Transport An active transport pump maintains an chemical gradient necessary for a different transporter or channel to function properly http://biomedicum.ut.ee/armpgb/1kursus/ani_6.swf
Secondary Active Transport Mechanism of the SGLT Transporter 1 Na + binds to carrier. Lumen of intestine or kidney Na + Glu Intracellular fluid SGLT protein 3 Glucose binding changes carrier conformation. Na + Glu [Na + ] high [Glucose] low [Na + ] low [Glucose] high 4 Na + released into cytosol. Glucose follows. 2 Na+ binding creates a site for glucose. Na + Glu Na + Glu Without a primary active transporter somewhere else in the membrane to move Na + to lumen, concentration gradient for Na + will be lost and SGLT can t operate Without a primary active transporter somewhere else in the membrane to move Na + to ECF, concentration gradient for Na + will be lost and SGLT can t operate
Lumen of intestine Na + high Glucose low Na + high Na + low Glucose high Na + low Glucose high Epithelial cell lining small intestine Na + low Na - high Glucose low Glucose high Na - high Na + K + pump (active) Primary Active Transport maintains Na + concentration gradient from lumen to cell, which drives Na+ K+ pump uses energy Secondary Active Transport Glucose low Blood vessel creating glucose concentration gradient from cell to blood used for GLUT (passive) Facilitated Diffusion 1 2 SGLT uses Na+ concentration 3 GLUT passively moves to drive Na+ uphill out of cell. gradient to simultaneously move Na+ downhill and glucose uphill from lumen into cell. glucose downhill out of cell into blood. Fig. 3-17a, p. 61 Glucose low Na + high Glucose low Na + high SGLT Glucose high Na + low Glucose high Na + low 2a Binding of Na+ on luminal side, where Na+ concentration is higher, increases affinity of SGLT for glucose. Therefore, glucose also binds to SGLT on luminal side, where glucose concentration is lower. 2b When both Na+ and glucose are bound, SGLT changes shape, opening to cell interior. 2c SGLT releases Na+ to cell interior, where Na+ concentration is lower. Because affinity of SGLT for glucose decreases on release of Na+, SGLT also releases glucose to cell interior, where glucose concentration is higher. Fig. 3-17b, p. 61
Vesicular Transport Material moves in/out of cell wrapped in membrane Active method of membrane transport Two types of vesicular transport Endocytosis Exocytosis
Vesicular Transport Two types of vesicular transport Endocytosis Process by which substances move into cell Pinocytosis nonselective uptake of stufff in ECF to get it INTO INTRACELLULAR Phagocytosis selective uptake of multimolecular particle to get it INTO INTRACELLULAR Exocytosis Provides mechanism for secreting large polar molecules that EXIT the cell to EXTRACELLULAR ENVIRONMENT Technically also Enables cell to add specific components to cell membrane Table 3-2, p. 63
END OF TEST MATERIAL